This project uses magnetic resonance imaging (MRI) to investigate the long-term consequences and potential brain toxicity resulting from use of the recreational drug 3,4-methylenedioxymethamphetamine (MDMA), also known as Ecstasy, in human subjects. Evidence from animal studies indicates that MDMA destroys fine-diameter serotonergic axons that arise from brainstem serotonergic neuron groups. Serotonin is important in a wide variety of brain functions including mood, memory, movement, eating, sleeping, pain, and sexual function. Studies examining neuropsychiatric function in MDMA users have shown that MDMA users have impaired memory and may have greater levels of impulsivity. Other studies examining brain structure and function in MDMA users have suggested that use of MDMA damages the serotonin system in humans, much like it does in animal models. Our goals are to determine whether or not MDMA use is associated with structural and chemical brain changes that correlate with impaired brain function. We will use the functional MRI blood oxygen level dependent (BOLD) method to study brain function in two domains: visual system activation to red and blue light (as a sensory modality) and frontal and temporal brain activation during a semantic word learning and recall task (as a cognitive modality). We hypothesize that MDMA users will have reduced brain activation in the visual cortex to red and blue light stimulation. We hypothesize that MDMA users will show decreased activation in left Brodmann's Areas (BA) 45 and 21 during the word-learning and recall task. Because axon death can result in gliosis, we hypothesize that MDMA users will have higher levels of myoinositol (MI), (a chemical that may serve as a marker for gila) in a magnetic resonance spectroscopy (MRS) study. Because neurons contain the neuronal marker N-acetylaspartate (NAA), we hypothesize that NAA will be decreased in MDMA users due to loss of serotoninlinked growth factor production, resulting in smaller neurons. We will also use the voxel-based-morphometry (VBM) method to determine whether MDMA users have areas of reduced gray matter concentration and volume. We hypothesize that MDMA users will have areas of reduced gray matter concentration and volume that will correlate with areas of reduced activation in the fMRI studies and altered metabolite concentrations in the MRS studies.